Global developmental delay and intellectual disability in the era of genomics: Diagnosis and challenges in resource limited areas

Abstract

AimsTo report the diagnostic yield of clinical singleton whole exome sequencing (WES) performed among a group of Jordanian children presenting with global developmental delay /intellectual disability (GDD/ID), discuss the underlying identified genetic disorders and the challenges encountered. Patients and methodsThis retrospective medical record review study included 154 children who were diagnosed with GDD/ID at our clinic at Jordan University Hospital between 2016 and 2021, and whose diagnostic work up included WES. ResultsConsanguinity among parents was reported in 94/154 (61.0%) patients and history of other affected siblings in 35/154 (22.7%) patients.Pathogenic and likely pathogenic variants (solved cases) were reported in 69/154 (44.8%) patients, a variant of uncertain significance was reported in 54/154 (35.0%) and a negative result was reported in 31/154 (20.1%) cases.In the solved cases, autosomal recessive diseases were the most common (33/69; 47.8%). Metabolic disorders were identified in 20/69 (28.9%) patients, followed by developmental and epileptic encephalopathies (9/69; 13.0%) and MECP2 related disorders (7/69; 10.1%). Other single gene disorders were identified in 33/69; 47.8%) patients. ConclusionThis study had several limitations, as it was hospital-based and only including patients who were able to afford the test. Nevertheless, it yielded several important findings. In resource-limited countries, WES may be a reasonable approach. We discussed the challenges that clinicians meet in the context of shortage of resources.